Aptamers in therapeutics ? (Why not)

Why are there not more aptamer based therapeutics? 

This blog by Drew Smith in 2019 nails a lot of the reasons, and in particular the issues related to the rapid clearance of aptamers from the body. https://drewsmithblog.com/2019/05/aptamers-still-looking-for-euphoria-in-the-wrong-places/. He effectively points out that the aptamer that he was involved with, and still the only aptamer that has been successfully commercialized as a therapeutic, Macugen, works well because it is injected into eyes, and thus it is not cleared as rapidly through the renal system. 

Potential ways to address this issue is to capitalize on the low toxicity and lack of immunogenicity of aptamers to increase the concentration applied, or to apply the aptamers on an ongoing slow release basis. I end up saying a similar thing in almost all blogs, in order to get aptamers to work effectively we need to stop thinking of them as oligonucleotide antibodies. 

It is clear that monoclonal antibodies (MAbs) have represented a tremendous success story for the pharmaceutical industry. In every case that I can think of the MAb works by inducing an immune response to a targeted molecule. This is something that MAbs are intrinsically better suited to do than aptamers. We are not going to succeed with aptamers in therapeutics by trying to make them work better than antibodies at what antibodies have evolved over millennia to do well. 

There are numerous disease indications or applications where an immune response is not what is desired. This is where aptamers can and should be directed for therapeutic application. Through our work on Alzheimer’s disease at our subsidiary in Paris, NeoNeuro (www.neoneuro-aptamers.com) we have realized that many of those afflicted exhibit symptoms of chronic inflammation of the brain. It is possible that increasing immune response to cells containing prion like proteins may actually accelerate the spread of neural degradation. In indications like this, or for gastro-intestinal disorders involving immune responses aptamer therapies may offer a better route than Mab therapies by blocking the immune response. 

One final point in response to the question of why are there not more aptamer based therapeutics is to simply point at the number of antibody therapies that fail. Developing any therapeutic is incredibly risky, and failures abound. If the pipeline for aptamers being developed for therapeutics was anywhere near as large there would be more successes. Even with the high risk and high cost of therapeutic development there is still a niche for aptamers. At NeoVentures we assess the feasibility of any potential  aptamer application before undertaking a project. If we do not think an aptamer solution is commercially feasible we will tell you. 

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